Considerable evidence has been accumulated which indicates that the ultimate carcinogens of polycyclic aromatic hydrocarbons (PAH's) are diol-epoxides. In order to gain additional insight into the mechanism of activation of PAH's we propose to study the metabolism and binding of 3-methylcholanthrene (3-MC). The major dihydrodiols of 3-MC do not appear to arise from 3-MC directly but from a metabolite, namely 1-hydroxy-3-methylcholanthrene. The aims of this proposal are to: (1) Measure the metabolism and binding (to exogenously added DNA) of 3-MC, 1-OH-3-MC and 2-OH-3-MC by lung microsomes, (2) measure the metabolism and binding of 3-MC, 1-OH-3-MC and 2-OH-3-MC using a perfused lung system, (3) measure the binding of 3-MC, 1-OH-3-MC, and 2-OH-3-MC to livers and lungs of susceptible and resistant mice, and (4) determine if 1-OH-3-MC and 2-OH-3-MC are formed stereospecifically. With these experiments we hope to determine the metabolic fate of 3-MC and the metabolites responsible for binding to DNA. These experiments will determine if benzylic hydroxylation of 3-MC is a prerequisite of carcinogenicity. These investigations are designed to increase our understanding of the mechanism of metabolic activation in relation to chemical carcinogenesis.